Scissors are still in chaos, the inextricable connection between diabetes and atrial fibrillation

Atrial fibrillation, diabetes, and chronic kidney disease (CKD) are three global epidemics that have a significant impact on the morbidity and mortality of patients
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Diabetes is not only a risk factor for atrial fibrillation, it is also a risk factor for thrombosis, comorbidities and mortality in patients with atrial fibrillation
.

What is the connection between diabetes and atrial fibrillation? When atrial fibrillation encounters diabetes, what "sparks" will it collide with? This article summarizes this
.

 Key points ➤Patients ≥65 years of age should undergo opportunistic screening for atrial fibrillation by pulse or electrocardiogram.
However, considering the risk of diabetic patients, it should be used with caution
.

 ➤For patients ≥75 years of age or at high risk of stroke, systematic ECG screening should be considered to detect the risk of atrial fibrillation
.

Given the risk of atrial fibrillation in diabetic patients, this is particularly worth considering
.

 ➤For patients with atrial fibrillation who have diabetes and at least one stroke risk factor (CHA2DS2-VASc), oral anticoagulants should be initiated to prevent the risk of stroke
.

 ➤In the case of insufficient blood glucose control, patients with atrial fibrillation with diabetes but no other stroke risk factors (CHA2DS2-VASc) should take anticoagulant drugs to prevent stroke
.

 ➤Patients with well-controlled diabetes and atrial fibrillation who have no other CHA2DS2-VASc stroke risk factors can take anticoagulants orally to prevent stroke
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Including type 1 diabetes patients (T1DM) younger than 65 years old
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 ➤Except for patients with mechanical valve replacement or mild-to-moderate mitral stenosis, patients with atrial fibrillation should give priority to direct oral anticoagulant (DOAC) instead of warfarin to prevent stroke
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 ➤A formal, structured bleeding risk score (HAS-BLED score) helps to identify the changeable or unchangeable risk factors for bleeding in patients with diabetes and atrial fibrillation, and to identify patients who need closer follow-up
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 Diabetes is a risk factor for atrial fibrillation 1.
Diabetes is a risk factor for atrial fibrillation.
Although there are few studies related to the risk of atrial fibrillation in T1DM patients, recent large-scale analytical trials have confirmed that T1DM is independently associated with a higher incidence of atrial fibrillation
.

For T2DM, studies have shown that compared with non-diabetic patients, the incidence of atrial fibrillation in diabetic patients is at least two times higher, and the incidence of atrial fibrillation in patients with microvascular complications (such as retinopathy and nephropathy) is or higher
.

 Insulin resistance may be a mechanism by which hypertension and obesity increase the risk of atrial fibrillation
.

Diabetes and impaired glucose tolerance are associated with an increased risk of left ventricular hypertrophy (LVH), which may also be one of the factors that promote the occurrence/development of atrial fibrillation
.

In addition, long-term inflammation may also be linked to diabetes and atrial fibrillation
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  Figure 1 The pathophysiological correlation of diabetes, atrial fibrillation and stroke Figure 2 The interaction between atrial fibrillation, diabetes and CKD Note: They are regarded as coexisting diseases: about 35% of patients with atrial fibrillation have CKD; about 30 % Of patients with atrial fibrillation have diabetes
.

 2.
Diabetes is a risk factor for mortality, complications and more symptoms of atrial fibrillation.
Diabetes and atrial fibrillation often coexist (Figure 2).
At this time, patients experience all-cause death, cardiovascular death, stroke, chronic kidney disease and heart failure The risk has increased significantly
.

Compared with patients with atrial fibrillation without diabetes, patients with atrial fibrillation with diabetes have an increased risk of death by 25%-60%
.

ORBIT-AF observational studies confirm this view.
Studies have shown that diabetes can worsen all-cause death, cardiovascular death, and multiple other cardiovascular event endpoints in patients with atrial fibrillation
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In addition, risk factors related to diabetes (such as high blood pressure and obesity) often worsen the prognosis
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Diabetes and decreased renal function are also closely related to an increased risk of cardiovascular disease
.

 It is worth noting that the risk of cardiovascular events and death in patients with atrial fibrillation is significantly increased when diabetes and renal function damage are combined at the same time, suggesting the importance of preventing cardiovascular events in such patients
.

 In diabetic patients, atrial fibrillation can be regarded as a sign of poor prognosis, and the risk of stroke in such patients is significantly increased, suggesting that all risk factors should be dealt with in a timely and active manner
.

In the absence of other comorbidities, the annual incidence of stroke in isolated diabetes is approximately 2.
2%
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 In addition to the increased risk of death and cardiovascular events, the presence of diabetes can also change the symptoms of patients with atrial fibrillation, especially dyspnea
.

The functional status of atrial fibrillation patients with diabetes is also worse
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In addition, diabetes can be used as an independent predictor of atrial fibrillation recurrence after ablation
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 3.
Atrial fibrillation screening in diabetic patients As the prevalence of atrial fibrillation in diabetic patients is high, diabetic patients should be actively screened for atrial fibrillation to identify and manage atrial fibrillation early
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 For patients with palpitations (or fatigue and dyspnea) symptoms (related to persistent or permanent atrial fibrillation), the diagnosis may be made during the outpatient clinic or hospitalization if the patient seeks urgent medical attention
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However, 30%-50% of patients with atrial fibrillation may have no symptoms
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It can be found in different ways, such as regular physical examination or 12-lead ECG during hospitalization, 24h or 72h Holter and remote monitoring
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 In addition, the subcutaneously implanted loop recorder can also help diagnose symptomatic or asymptomatic atrial fibrillation, but most countries only approve it for the evaluation of unexplained syncope or ischemic stroke patients (with known atrial fibrillation)
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However, implanting an implantable loop recorder in diabetic patients to detect the efficacy of atrial fibrillation may have a similar clinical outcome as oral anticoagulation therapy
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 Currently, atrial fibrillation can be detected by consumer devices and wearable devices (such as photoplethysmography) that detect irregular pulses
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At this time, the diagnosis of atrial fibrillation can be confirmed through ECG recording or direct ECG tracking (such as using Apple watch)
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 At present, there is no specific recommendation for routine screening of atrial fibrillation in asymptomatic diabetic patients, but the following two points should be clarified: ①When diabetes is related to other risk factors, that is, when the CHA2DS2-VASc score is high, atrial fibrillation occurs during the follow-up period.
The risk of fibrillation is increased.
In the high-risk subgroup, nearly 40% of patients will develop atrial fibrillation within 2 years
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②At the same time, the risk of thromboembolism in these patients with atrial fibrillation increases exponentially, reaching 8%-10% every year
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 In addition, on the population scale, in order to reduce the risk of stroke, it seems reasonable to screen for atrial fibrillation in patients with a CHA2DS2-VASc score ≥2, but this method has not been confirmed in a randomized trial
.

However, the "ESC Guidelines for the Management of Atrial Fibrillation" recommends that patients ≥65 years of age should undergo opportunistic screening for atrial fibrillation.
Therefore, it is obviously reasonable for diabetic patients to undergo systemic or opportunistic screening for atrial fibrillation
.

 Clinical complications of atrial fibrillation combined with diabetes 1.
Increased risk of cerebrovascular and cardiovascular complications when diabetes combined with atrial fibrillation Diabetes is a life>
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In addition, T1DM and T2DM are associated with an increased risk of stroke, but patients with T1DM have a lower risk
.

 It is worth noting that the type of stroke associated with diabetes is different from the type of stroke associated with atrial fibrillation
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Most strokes in diabetic patients are ischemic rather than hemorrhagic, and the most common type is lacunar infarction, which is associated with the coexistence of microvascular disease and hypertension
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 In addition, diabetes-related stroke mortality is higher, and the risk of stroke recurrence and stroke-related dementia is also higher
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  Figure 3 Stroke risk assessment in diabetic patients without other stroke risk factors (male with CHA2DS2-VASc score 1 and female with 2 points) 2.
Diabetes subtypes, severity and risk of atrial fibrillation A characteristic heterogeneous chronic metabolic disease, which may be caused by several different mechanisms, such as low insulin production and/or reduced insulin sensitivity
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 Generally, T1DM (10%-15%) has a younger age of onset and is characterized by a lack of insulin production related to autoimmunity; T2DM (80-85%) has an older age of onset and is characterized by insulin resistance (related to obesity) ) Related to higher circulating insulin levels
.

In addition, there are other rare forms of diabetes, such patients usually have a genetic background, such as adult-onset diabetes (MODY) and neonatal diabetes
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 It has been confirmed that patients with T1DM and T2DM have an increased risk of atrial fibrillation, and the additional risk of atrial fibrillation in patients with 12DM and T2DM increases with worsening blood glucose and renal complications
.

 The 2020 ESC Guidelines for the Diagnosis and Treatment of Atrial Fibrillation pointed out that the risk of stroke related to atrial fibrillation and diabetes is similar in patients with T1DM and T2DM; however, compared with patients with T1DM younger than 65 years old, the risk of T2DM patients is slightly increased
.

 A Danish registered study followed up for 3 years and showed that there was no difference in the risk of thromboembolism in patients with T1DM and T2DM (adjusted HR=1.
15, 95%CI: 0.
91–1.
44)
.

Age stratification analysis showed that in patients <65 years of age, the HR of T2DM was 1.
97 (95%CI: 1.
07–3.
61) compared with T1DM; but there was no difference in the elderly population
.

 In addition, diabetes is also heterogeneous.
In addition to the type of diabetes, different degrees of target organ damage (eyes, nerves, and kidneys) can also lead to different risks of cardiovascular complications
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The risk of stroke in patients with diabetes and atrial fibrillation also increases with the duration of diabetes and diabetic complications (such as nephropathy and retinopathy)
.

 Finally, gestational diabetes is not related to the occurrence of atrial fibrillation, but it can significantly increase the risk of T2DM in the later stages
.

 The impact of anticoagulation therapy on patients with diabetes and atrial fibrillation Oral anticoagulation therapy can significantly reduce the risk of stroke and systemic embolism in high-risk patients
.

At present, it is generally believed that the efficacy of anticoagulation therapy is better than that of antiplatelet drugs
.

 Patients with atrial fibrillation should be stratified according to the risk of stroke and systemic embolism
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At present, the preferred risk stratification scheme for cardiac embolism (recommended by the ESC and ACC/AHA guidelines) is the CHA2DS2-VASc score, especially to exclude patients with a sufficiently low risk of stroke from anticoagulation therapy
.

As the possibility of thromboembolic events in patients with atrial fibrillation combined with diabetes is significantly increased, this score considers diabetes as a risk factor for stroke
.

 Warfarin treatment in diabetic patients can significantly reduce stroke and systemic embolism events, but diabetic patients are more likely to have adverse bleeding events
.

 Because diabetes is a risk factor in the stroke risk score that determines whether patients with atrial fibrillation should be treated with anticoagulation, many diabetic patients receive anticoagulation therapy
.

Since diabetes is the strongest factor in the CHA2DS2-VASc score of 1 point, it may be recommended for every diabetic patient with atrial fibrillation to undergo anticoagulation therapy, especially when diabetes has occurred for a period of time
.

 In addition, because randomized controlled trials have shown that DOAC is more effective, it is recommended that patients with diabetes choose DOAC instead of warfarin
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 Yimaitong compiled from: Laurent Fauchier, Giuseppe Boriani, Joris R de Groot, et al.
Medical therapies for prevention of cardiovascular and renal events in patients with atrial fibrillation and diabetes mellitus.
EP Europace.
2021; 23(12): 1873– 1891.